Quaternary Ammonium compounds phase-transfer catalysts

There are a number of industrially important reactions where two liquid phases are involved and the aqueous phase contains ionic species. Here the rate may be severely limited due to low solubiblity of the reactant, located in the organic phase, in water. We would benefit from using a pha.se-transfer (PT) catalyst, which ferries the ionic species into the organic phase thus overcoming a severe limitation. Such PT catalysts are typically quaternary ammonium compounds like tetrabutylammonium halides, trioctylmethylammonium chloride, etc. (see also Section 3.8). 

Benzylic quaternary phosphonium and ammonium salts are dealky-lated by mild heating and/or nucleophilic anions, particularly iodide (9) and thiolate (10), but also hydroxide (11). Most N-benzyl-pyridinium or quaternary aryl ammonium compounds are particularly susceptible (12). Decompositions of this sort have seriously limited the usefulness of solid phase-transfer catalysts derived from (chloromethyl)polystyrene (13, 14). 

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

The preparation of novel phase transfer catalysts and their application in solving synthetic problems are well documented(l). Compounds such as quaternary ammonium and phosphonium salts, phosphoramides, crown ethers, cryptands, and open-chain polyethers promote a variety of anionic reactions. These include alkylations(2), carbene reactions (3), ylide reactions(4), epoxidations(S), polymerizations(6), reductions(7), oxidations(8), eliminations(9), and displacement reactions(10) to name only a few. The unique activity of a particular catalyst rests in its ability to transport the ion across a phase boundary. This boundary is normally one which separates two immiscible liquids in a biphasic liquid-liquid reaction system. 

A compound whose addition to a two-phase organic water system helps to transfer a water soluble ionic reactant across the interface to the organic phase where a homogeneous reaction can take place is called a phase transfer catalyst. These catalysts enhance the rate of a reaction. A quaternary ammonium halide R4N+ X- e.g., tetrabutylammonium halide is phase transfer catalyst. It can cause the transfer of the... 

Quaternary ammonium salts of heterocyclic compounds have been used in liquid-liquid phase-transfer syntheses. When these compounds are achiral, they show a behavior very similar to that of other quaternary ammonium salts. For example, 2-dialkylamino-l-alkylpyridinium tetrafluoroborates have been used by Tanaka and Mukayama282 in the alkylation of active methylene compounds PhCH2CN, PhCH(Et)CN, and PhCH(Me)COPh. However, comparative studies of the efficiency of the catalysts show that alkylpyridinium bromides283 or N-alkyl-Af-benzyl-piperidinium chloride284 have a smaller catalytic activity compared to tetraalkylammonium halides. McIntosh285 has described the preparation of azapropellane salts 186 as potential chiral phase transfer catalysts. 

Darzens condensation of chloroacetonitrile and carbonyl compounds to give glycidic nitriles can be carried out in the presence of aqueous sodium hydroxide and a quaternary ammonium catalyst, such as triethylbenzylammonium chloride (TEBA equation 32). In a subsequent study, interesting stereochemical control was obtained in an interfacial Darzens condensation. Condensation of a-chloro-phenylacetonitrile (93) with benzaldehyde, conducted in benzene in the presence of 50% aqueous sodium hydroxide and TEBA as a phase transfer catalyst, affords predominantly the traru-glycidonitrile (94) accompanied by the corresponding cis isomer (95 equation 33). Similar results are obtained when... 

Several quaternary ammonium compounds are used in organic chemistry as phase-transfer catalysts. The mechanism of the catalytic process can be represented by a combination of phase-transfer and ion-exchange equilibria. In the case of substitution reactions in two-phase systems, the negatively charged nucleophile is extracted by the positive ammonium ion from the aqueous phase into the organic phase where substitution takes place (Makosza and rafin, 1965, Makosza, 1969, Dockx, 1973). 

Quaternary ammonium salts derived from ephedrine have been used as catalysts for the addition of dialkylzinc to carbonyl compounds (Section D.1.3.1.4.) and are useful as phase-transfer catalysts for alkylation of carbonyl compounds17 and reductions18. N-Benzyl-A -methylephedri-nium salts 10 have found varied application they are easily prepared from A -methylephedrine 913 by reaction with benzyl halide in toluene1 or chloroform/methanol (1 1)18 in high yield. Ref 18 also gives the preparation of other ephedrinium and pseudoephedrinium salts. 

Quaternary ammonium salts, compounds of the type R4N X , find application as phase-transfer catalysts. A small amount of a quaternary ammonium salt promotes the transfer of an anion from aqueous solution, where it is highly solvated, to an organic solvent, where it is much less solvated and much more reactive. 

It was considered previously that the most effective phase transfer catalysts are quaternary ammonimn bases. However, preliminary experiments with crown-ethers had already shown that these compounds are more powerful phase transfer catalysts than quaternary ammonium bases and are more selective [106, 177]. This is explained by differences in the mechanism of catalytic action. The mechanisms of reaction acceleration in two-phase systems with crown-ethers are as yet little studied, but simple examination of salt extraction with crown-ethers shows that the salt in the aqueous phase G>oth anion and cation) passes into the organic layer, whereas only anions paired with the onium cation pass from the aqueous into the organic phase during extraction with onium salts. This considerable difference in the mechanism of action of the two groups of ion-carrying catalysts is the basis for the prospective use of crown-ethers and their analogs instead of quaternary ammonium bases in many fields. 

Quaternary ammonium salts, PEGs and crown ethers are the eommon compounds, employed as PTC. The inexpensive tertiary amines have also been used as the phase transfer catalysts (PTC) in recent years. The synthetic process for producing 2-mercaptobcnzimidazolc (MBI) is a reaction of o-phenylene diamine (C6H4(NH2)2) and carbon disulfide (CSj) in a two-phase medium affected by appropriate choice of solvent. 

The technique of phase-transfer catalysis has been extensively apphed to the two-phase polycondensation using various phase-transfer catalysts, such as quaternary ammonium and phosphonium salts, crown ethers and poly(ethylene glycol)s. 5 - 53,75,87,n9,i5i Various types of condensation polymers such as aromatic polysulfonates and polysulfides, aromatic polyethers, ahphatic and aromatic polysulfides, and carbon-carbon chain polymers of high molecular weights hy the phase-transfer catalyzed polycondensation fi-om combinations of aromatic disulfonyl chlorides, phosphonic dichlorides, activated aromatic dichlorides, and aliphatic dihahdes, with bisphenol, aliphatic and aromatic dithiols, and active ethylene compounds. The two-phase polycondensation was generally carried out in a water-immiscible organic solvent-aqueous alkaline solution system at room temperature. The method of polycondensation offers a highly versatile and convenient synthetic method for a variety of condensation polymers. 

New and efficient catalysts for the epoxidation of unactivated olefins wifli hydrogen peroxide have been discovered in recent years (9). These are classified in two groups phase transfer catalysts 10) and metal-substituted zeolites (77). Phase transfer catalysts, such as for example W04 /HjP04/R4N are composed by the association of tungstic and phosphoric acids with a quaternary ammonium or phosphonium compound. Titanium silicalite (TS-1) is the most effective catalyst of the second group. The performances of other metal-substituted zeolites in the epoxidation of olefins are still unsatisfactoiy (9). 

Linear olefinic [242] and acetylenic [243] compounds are readily bromi-nated by H202/HBr at ambient temperature, as shown in the above example. Cyclohexene can be chlorinated or brominated in two phases (H2O/CCI4) using a quaternary ammonium phase-transfer catalyst under mild conditions [244]. 

In auxiliary- and substrate-controlled Sj Ar reactions, stoichiometric amounts of enantiomeri-cally pure compounds are required. In recent years, major progress has come from the development of chiral catalyzed reactions (Section 8.3). In the approach conceptualized by Tomioka (Section 8.3.1), the formation of a new stereogenic unit is induced by substoichiometric or catalytic amounts of a chiral neutral ligand able to chelate the nucleophile. Jprgensen and Maruoka have shown that chiral quaternary ammonium and phosphonium cations Q can induce asymmetry during the Sj Ar process by acting as chiral phase-transfer catalysts (Section 8.3.2). Finally, recent advances in absolute asymmetric Sj Ar rely on new developments in homochiral crystallization (Section 8.4). 

One final note regarding the use of crown ethers as phase transfer catalysts there is little literature which directly compares quaternary ammonium catalysts with crown ethers in liquid-liquid processes (see Sect. 1.10) [48]. There are examples where both have been tried and are effective. In general, however, it appears that for solid-liquid phase transfer processes, the crowns are far better catalysts than are the quaternary ammonium ions. In order for a solid-liquid phase transfer process to succeed, the catalyst must remove an ion pair from a solid matrix. The quaternary catalysts have no chelating heteroatoms with available lone pairs which would favor such a process. The combination of a quaternary catalyst and some simple coordinating amine or ether would probably succeed [28, 32, 34]. It seems likely, as mentioned above, that it is the combination of diamine and quaternary catalyst generated in situ which accounts for the success of Normanf s catalysts [28]. It is interesting to speculate on the possibility of using a quaternary ammonium compound and a drop of water as a catalytic system. 

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